Skip to main content
Top
Published in: Pediatric Nephrology 12/2007

01-12-2007 | Original Article

NGAL is an early predictive biomarker of contrast-induced nephropathy in children

Authors: Russel Hirsch, Catherine Dent, Holly Pfriem, Janene Allen, Robert H. Beekman III, Qing Ma, Sudha Dastrala, Michael Bennett, Mark Mitsnefes, Prasad Devarajan

Published in: Pediatric Nephrology | Issue 12/2007

Login to get access

Abstract

We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of contrast-induced nephropathy (CIN). We prospectively enrolled 91 children (age 0–18 years) with congenital heart disease undergoing elective cardiac catheterization and angiography with contrast administration (CC; Ioversol). Serial urine and plasma samples were analyzed in a double-blind fashion by NGAL enzyme-linked immunosorbent assay (ELISA). CIN, defined as a 50% increase in serum creatinine from baseline, was found in 11 subjects (12%), but detection using increase in serum creatinine was only possible 6–24 h after CC. In contrast, significant elevation of NGAL concentrations in urine (135 ± 32 vs. 11.6 ± 2 ng/ml without CIN, p < 0.001) and plasma (151 ± 34 vs. 36 ± 4 without CIN, p < 0.001) were noted within 2 h after CC in those subjects. Using a cutoff value of 100 ng/ml, sensitivity, specificity, and area under the receiver-operating characteristic (ROC) curve for prediction of CIN were excellent for the 2-h urine NGAL (73%, 100%, and 0.92, respectively) and 2-h plasma NGAL (73%, 100%, and 0.91, respectively). By multivariate analysis, the 2-h NGAL concentrations in the urine (R 2 = 0.52, p < 0.0001) and plasma (R 2 = 0.72, p < 0.0001) were found to be powerful independent predictors of CIN. Patient demographics and contrast volume were not predictive of CIN.
Literature
1.
go back to reference Goldstein SL (2006) Pediatric acute kidney injury: it’s time for real progress. Pediatr Nephrol 21:891–895CrossRef Goldstein SL (2006) Pediatric acute kidney injury: it’s time for real progress. Pediatr Nephrol 21:891–895CrossRef
3.
go back to reference Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39:930–936CrossRef Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39:930–936CrossRef
4.
go back to reference Pannu N, Wiebe N, Tonelli M (2006) Prophylaxis strategies for contrast-induced nephropathy. JAMA 295:2765–2779CrossRef Pannu N, Wiebe N, Tonelli M (2006) Prophylaxis strategies for contrast-induced nephropathy. JAMA 295:2765–2779CrossRef
5.
go back to reference McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J, CIN Consensus Working Panel (2006) Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol 98(Suppl):5K–13KCrossRef McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J, CIN Consensus Working Panel (2006) Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol 98(Suppl):5K–13KCrossRef
6.
go back to reference McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J, CIN Consensus Working Panel (2006) Risk prediction of contrast-induced nephropathy. Am J Cardiol 98(Suppl):27K–36KCrossRef McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J, CIN Consensus Working Panel (2006) Risk prediction of contrast-induced nephropathy. Am J Cardiol 98(Suppl):27K–36KCrossRef
7.
go back to reference Hui-Stickle S, Brewer ED, Goldstein SL (2005) Pediatric ARF epidemiology at a tertiary care center from 1999–2001. Am J Kidney Dis 45:96–101CrossRef Hui-Stickle S, Brewer ED, Goldstein SL (2005) Pediatric ARF epidemiology at a tertiary care center from 1999–2001. Am J Kidney Dis 45:96–101CrossRef
8.
go back to reference Solomon R (2007) Contrast media nephropathy - how to diagnose and how to prevent? Nephrol Dial Transplant 22:1812–1815CrossRef Solomon R (2007) Contrast media nephropathy - how to diagnose and how to prevent? Nephrol Dial Transplant 22:1812–1815CrossRef
9.
go back to reference Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182PubMed Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182PubMed
10.
go back to reference Devarajan P (2007) Emerging biomarkers of acute kidney injury. Contrib Nephrol 156:203–212CrossRef Devarajan P (2007) Emerging biomarkers of acute kidney injury. Contrib Nephrol 156:203–212CrossRef
11.
go back to reference Stacul F, Adam A, Becker CR, Davidson C, Lameire N, McCullough PA, Tumlin J (2006) Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol 98(Suppl):59K–77KCrossRef Stacul F, Adam A, Becker CR, Davidson C, Lameire N, McCullough PA, Tumlin J (2006) Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol 98(Suppl):59K–77KCrossRef
12.
go back to reference Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P (2003) Differential gene expression following early renal ischemia-reperfusion. Kidney Int 63:1714–1724CrossRef Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P (2003) Differential gene expression following early renal ischemia-reperfusion. Kidney Int 63:1714–1724CrossRef
13.
go back to reference Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of NGAL as a novel urinary biomarker for ischemic injury. J Am Soc Nephrol 4:2534–2543CrossRef Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of NGAL as a novel urinary biomarker for ischemic injury. J Am Soc Nephrol 4:2534–2543CrossRef
14.
go back to reference Devarajan P, Mishra J, Supavekin S, Patterson LT, Potter SS (2003) Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery and novel therapeutics. Mol Genet Metab 80:365–376CrossRef Devarajan P, Mishra J, Supavekin S, Patterson LT, Potter SS (2003) Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery and novel therapeutics. Mol Genet Metab 80:365–376CrossRef
15.
go back to reference Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P (2004) Neutrophil gelatinase-associated lipocalin (NGAL): a novel urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 24:307–315CrossRef Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P (2004) Neutrophil gelatinase-associated lipocalin (NGAL): a novel urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 24:307–315CrossRef
16.
go back to reference Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J, Devarajan P (2004) Amelioration of ischemic acute renal injury by NGAL. J Am Soc Nephrol 15:3073–3082CrossRef Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J, Devarajan P (2004) Amelioration of ischemic acute renal injury by NGAL. J Am Soc Nephrol 15:3073–3082CrossRef
17.
go back to reference Mori K, Lee HT, Rapoport D, Drexler I, Foster K, Yang J, Schmidt-Ott, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia. J Clin Invest 115:610–621CrossRef Mori K, Lee HT, Rapoport D, Drexler I, Foster K, Yang J, Schmidt-Ott, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia. J Clin Invest 115:610–621CrossRef
18.
go back to reference Mishra J, Ma Q, Kelly C, Mitsnefes M, Mori K, Barasch J, Devarajan P (2006) Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 21:856–863CrossRef Mishra J, Ma Q, Kelly C, Mitsnefes M, Mori K, Barasch J, Devarajan P (2006) Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 21:856–863CrossRef
19.
go back to reference Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury following cardiac surgery. Lancet 365:1231–1238CrossRef Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury following cardiac surgery. Lancet 365:1231–1238CrossRef
20.
go back to reference Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P (2006) Urine NGAL and IL-18 are predictive biomarkers for DGF following kidney transplantation. Am J Transplant 6:1639–1645CrossRef Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P (2006) Urine NGAL and IL-18 are predictive biomarkers for DGF following kidney transplantation. Am J Transplant 6:1639–1645CrossRef
21.
go back to reference Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P (2006) Urinary NGAL in D+HUS: A novel marker of renal injury. Pediatr Nephrol 21:989–994CrossRef Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P (2006) Urinary NGAL in D+HUS: A novel marker of renal injury. Pediatr Nephrol 21:989–994CrossRef
22.
go back to reference Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, Mishra J, Devarajan P (2006) Urinary NGAL as a biomarker of nephritis in childhood-onset SLE. Arthritis Rheum 54:2577–2584CrossRef Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, Mishra J, Devarajan P (2006) Urinary NGAL as a biomarker of nephritis in childhood-onset SLE. Arthritis Rheum 54:2577–2584CrossRef
23.
go back to reference Mitsnefes M, Kathman T, Mishra J, Kartal J, Khoury P, Nickolas T, Barasch J, Devarajan P (2007) Serum NGAL as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol 22:101–108CrossRef Mitsnefes M, Kathman T, Mishra J, Kartal J, Khoury P, Nickolas T, Barasch J, Devarajan P (2007) Serum NGAL as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol 22:101–108CrossRef
24.
go back to reference Xu S, Venge P (2000) Lipocalins as biomarkers of disease. Biochim Biophys Acta 1482:298–307CrossRef Xu S, Venge P (2000) Lipocalins as biomarkers of disease. Biochim Biophys Acta 1482:298–307CrossRef
25.
go back to reference Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, Devarajan P, Barasch J (2006) NGAL-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 15:442–449CrossRef Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, Devarajan P, Barasch J (2006) NGAL-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 15:442–449CrossRef
26.
go back to reference Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18:407–413CrossRef Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18:407–413CrossRef
27.
go back to reference Liu Q, Nilsen-Hamilton M (1995) Identification of a new acute phase protein. J Biol Chem 270:22565–22570CrossRef Liu Q, Nilsen-Hamilton M (1995) Identification of a new acute phase protein. J Biol Chem 270:22565–22570CrossRef
28.
go back to reference Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S (2006) Neutrophil gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol 26:287–292CrossRef Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S (2006) Neutrophil gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol 26:287–292CrossRef
29.
go back to reference Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S (2007) Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and eGFR in patients with normal serum creatinine undergoing coronary angiography. Nephrol Dial Transplant 22:295–296CrossRef Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S (2007) Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and eGFR in patients with normal serum creatinine undergoing coronary angiography. Nephrol Dial Transplant 22:295–296CrossRef
30.
go back to reference Herget-Rosenthal S, Marggraf G, Husing J, Goring F, Pietruck F, Janssen O, Philipp T, Kribben A (2004) Early detection of acute renal failure by serum cystatin C. Kidney Int 66:1115–1122CrossRef Herget-Rosenthal S, Marggraf G, Husing J, Goring F, Pietruck F, Janssen O, Philipp T, Kribben A (2004) Early detection of acute renal failure by serum cystatin C. Kidney Int 66:1115–1122CrossRef
31.
go back to reference Duan SB, Wu HW, Luo JA, Liu FY (1999) Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media. Nephron 83:122–125CrossRef Duan SB, Wu HW, Luo JA, Liu FY (1999) Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media. Nephron 83:122–125CrossRef
32.
go back to reference Hampel DJ, Sansome C, Sha M, Brodsky S, Lawson WE, Goligorsky MS (2001) Toward proteomics in uroscopy: urinary protein profiles after radiocontrast medium administration. J Am Soc Nephrol 12:1026–1035PubMed Hampel DJ, Sansome C, Sha M, Brodsky S, Lawson WE, Goligorsky MS (2001) Toward proteomics in uroscopy: urinary protein profiles after radiocontrast medium administration. J Am Soc Nephrol 12:1026–1035PubMed
Metadata
Title
NGAL is an early predictive biomarker of contrast-induced nephropathy in children
Authors
Russel Hirsch
Catherine Dent
Holly Pfriem
Janene Allen
Robert H. Beekman III
Qing Ma
Sudha Dastrala
Michael Bennett
Mark Mitsnefes
Prasad Devarajan
Publication date
01-12-2007
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 12/2007
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-007-0601-4

Other articles of this Issue 12/2007

Pediatric Nephrology 12/2007 Go to the issue